Edex

INDICATIONS AND USAGE edex ® is indicated for the treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology.

DOSAGE AND ADMINISTRATION edex ® in the Treatment of Erectile Dysfunction The dosage range of edex ® for the treatment of erectile dysfunction is 1 to 40 mcg. The intracavernous injection should be given over a 5 to 10 second interval. In a study with a dose range of 1 to 20 mcg of edex ® , the mean dose was 10.7 mcg at the end of the dose titration period. In two studies with a dose range of 1 to 40 mcg of edex ® , the mean dose was 21.9 mcg at the end of the dose titration period. Doses greater than 40 mcg have not been studied. A 1⁄2-inch, 27- to 30-gauge needle is generally recommended for the intracavernous injection. The patient is advised not to exceed the optimum edex ® dose which was determined in the doctor's office. The lowest possible effective dose should always be used. Initial Titration in Physician's Office Erectile Dysfunction of Vasculogenic, Psychogenic, or Mixed Etiology : Dosage titration should be initiated at 2.5 mcg of alprostadil. If there is a partial response, the dose may be increased by 2.5 mcg to a dose of 5 mcg and then in increments of 5 to 10 mcg, depending upon erectile response, until the dose that produces an erection suitable for intercourse and not exceeding a duration of 1 hour is reached. If there is no response to the initial 2.5-mcg dose, the second dose may be increased to 7.5 mcg, followed by increments of 5 to 10 mcg. The patient must stay in the physician's office until complete detumescence occurs. If there is no response, then the next higher dose may be given within 1 hour. If there is a response, then there should be at least a 1-day interval before the next dose is given. Erectile Dysfunction of Pure Neurogenic Etiology (Spinal Cord Injury): Dosage titration should be initiated at 1.25 mcg of alprostadil. The dose may be increased by 1.25 mcg to a dose of 2.5 mcg, followed by an increment of 2.5 mcg to a dose of 5 mcg, and then in 5-mcg increments until the dose that produces an erection suitable for intercourse and not exceeding a duration of 1 hour is reached. The patient must stay in the physician's office until complete detumescence occurs. If there is no response, then the next higher dose may be given within 1 hour. If there is a response, then there should be at least a 1-day interval before the next dose is given. At-Home (Maintenance Therapy) Dosing Instructions The first injections of edex ® must be done at the physician's office by medically trained personnel. Self-injection therapy by the patient can be started only after the patient is properly instructed and well trained in the self-injection technique. The physician should instruct the patient to discard any needles which become bent during the self-injection procedure as these needles may break. The physician should make a careful assessment of the patient's skills and competence with the self-injection procedure. The intracavernous injection must be done under sterile conditions. The site of injection is usually along the lateral aspect of the proximal third of the penis. Visible veins should be avoided. The side of the penis that is injected and the site of injection must be alternated. The injection site must be cleansed with an alcohol swab before injection. The dose of edex ® that is selected for self-injection treatment should provide the patient with an erection that is satisfactory for sexual intercourse and that is maintained for no longer than 1 hour. If the duration of erection is longer than 1 hour, the dose of edex ® should be reduced. The lowest effective dose should be used at home. Self-injection therapy for use at home should be initiated at the dose that was determined in the physician's office. Dose adjustment may be required and should be made only after consultation with the physician. Careful and continuous follow-up of the patient while in the self-injection program must be exercised. This is especially true for the initial self-injections, since adjustments in the dose of edex ® may be n …

CONTRAINDICATIONS edex ® should not be used: in men who have conditions that predispose them to priapism, such as sickle cell anemia or sickle cell trait, multiple myeloma, or leukemia (see WARNINGS ) . for the treatment of erectile dysfunction in men with fibrotic conditions of the penis, such as cavernosal fibrosis or Peyronie’s disease (see PRECAUTIONS ) . in men with penile implants

ADVERSE REACTIONS edex ® , administered by intracavernous injection in doses ranging from 1 to 40 mcg per injection for periods up to 24 months, has been evaluated in clinical trials for safety in over 1,065 patients with erectile dysfunction. Discontinuation of therapy due to a side effect in clinical trials was required in approximately 9% of patients treated with edex ® and in 4 ≤ 6 Hours 44 (4) Faulty injection technique 3 59 (6) > 6 Hours 6 (<1) Penis disorder 28 (3) Bleeding 158 (15) Erythema 17 (2) Hematoma 56 (5) 1 Protocol Numbers KU-620-001, KU-620-002, KU-620-003, F-8653. 2 Penile pain reported without an association to injection site or erection, such as pain in penis and scrotum, pain in glans penis, and burning penile pain. 3 Examples include injection into glans penis, urethra or subcutaneously. Systemic Adverse Experiences The following systemic adverse experiences were reported in controlled and uncontrolled studies in ≥1% of patients treated for up to 24 months with edex ® . Systemic Adverse Experiences Reported by ≥1% of Patients 1 BODY SYSTEM edex ® BODY SYSTEM edex ® BODY SYSTEM edex ® Adverse Experience N = 1065 Adverse Experience N = 1065 Adverse Experience N = 1065 n (%) n (%) n (%) RESPIRATORY CARDIOVASCULAR UROGENITAL Upper respiratory tract Hypertension 17 (2) Prostate disorder 15 (1) infection 58 (5) Myocardial infarction 13 (1) Testicular pain 13 (1) Sinusitis 14 (1) Abnormal ECG 12 (1) Inguinal hernia 11 (1) BODY AS A WHOLE Influenza-like symptoms 35 (3) METABOLIC/NUTRITIONAL DERMATOLOGIC Headache 20 (2) Hypertriglyceridemia 17 (2) Skin disorder 14 (1) Infection 18 (2) Hypercholesterolemia 12 (1) SPECIAL SENSES Pain 16 (2) Hyperglycemia 12 (1) Abnormal vision 11 (1) MUSCULOSKELETAL Back pain 23 (2) Leg pain 13 (1) 1 Protocol Numbers KU-620-001, KU-620-002, KU-620-003, F-8653. Hemodynamic changes, manifested as increases or decreases in blood pressure and pulse rate, were observed during clinical studies but did not appear to be dose-dependent. Four patients (<1%) reported clinical symptoms of hypotension such as dizziness or syncope. edex ® had no clinically important effect on serum or urine laboratory tests. Post-Marketing Adverse Experiences Needle breakage.

Drug Interactions The pharmacodynamic interaction between heparin (5,000 units) and alprostadil intravenous infusion (90 mcg over 3 hours) was investigated. The results indicate significant changes in partial thromboplastin time (140% increase) and thrombin time (120% increase). Therefore, caution should be exercised with concomitant administration of heparin and edex ® . (Also, see Drug-Drug Interactions in CLINICAL PHARMACOLOGY, Pharmacokinetics .)

Mode of Action Alprostadil is a smooth muscle relaxant. Precontracted isolated preparations of the human corpus cavernosum, corpus spongiosum and cavernous artery are relaxed by alprostadil. Alprostadil has been shown to bind to specific receptors in human penile tissue. Two types of receptors that differ in their PGE 1 binding affinity have been identified. The binding of alprostadil to its receptors is accompanied by an increase in intracellular cAMP levels. Human cavernous smooth muscle cells respond to alprostadil by releasing intracellular calcium into the surrounding medium. Smooth muscle relaxation is associated with a reduction of the cytoplasmic free calcium concentration. Alprostadil also attenuates presynaptic noradrenaline release in the corpus cavernosum which is essential for the maintenance of a flaccid and non-erect penis. Alprostadil induces erection by relaxation of trabecular smooth muscle and by dilation of cavernous arteries. This leads to expansion of lacunar spaces and entrapment of blood by compressing the venules against the tunica albuginea, a process referred to as the corporal veno-occlusive mechanism.

DESCRIPTION edex ® (alprostadil for injection) is a sterile, pyrogen-free powder containing alprostadil in an alfadex (α-cyclodextrin) inclusion complex. Alprostadil is an endogenous substance known as prostaglandin E 1 (PGE 1 ). edex ® is supplied in single-dose, dual-chamber cartridges. edex ® is lyophilized in single-dose, dual-chamber cartridges intended for use with the reusable edex ® injection device. One chamber of the cartridge contains alprostadil, alfadex and lactose as a sterile, pyrogen-free powder. The other chamber contains 1.075 mL of sterile 0.9% sodium chloride. The edex ® cartridges are supplied in three strengths: 10-mcg cartridge (10.75 mcg alprostadil, 347.55 mcg α-cyclodextrin, 51.06 mg lactose); 20-mcg cartridge (21.5 mcg alprostadil, 695.2 mcg α-cyclodextrin, 51.06 mg lactose); 40-mcg cartridge (43 mcg alprostadil, 1,390.3 mcg α-cyclodextrin, 51.06 mg lactose). The edex ® injection device is used to reconstitute the sterile powder in one chamber with the sterile 0.9% sodium chloride in the other chamber. After reconstitution, the edex ® injection device is used to administer the intracavernous injection of alprostadil. The chemical name for alprostadil is (1R,2R,3R)-3-Hydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxocyclopentane heptanoic acid. The empirical formula is C 20 H 34 O 5 and the molecular weight is 354.49. The chemical structure is: The α-cyclodextrin inclusion complex improves the water solubility of alprostadil. The empirical formula of α-cyclodextrin is C 36 H 60 O 30 and the molecular weight is 972.85. The chemical structure is: Alprostadil alfadex is a white, odorless, hygroscopic powder. It is freely soluble in water and practically insoluble in ethanol, ethyl acetate and ether. After reconstitution, the active ingredient, alprostadil, immediately dissociates from the α-cyclodextrin inclusion complex. The reconstituted solution is clear and colorless and has a pH between 4.0 and 8.0. When the single-dose, dual-chamber cartridge containing either 10.75, 21.5, or 43 mcg of alprostadil is placed into the edex ® injection device and reconstituted, the deliverable amount of alprostadil in each milliliter is 10, 20 or 40 mcg, respectively. alprostadil chemical structure α-cyclodextrin chemical structure

OVERDOSAGE Limited data are available in regard to edex ® overdose in humans. Systemic reactions are uncommon with intracavernous injection of edex ® . Hypotension occurred in less than 1% of patients treated with edex ® . A single dose rising tolerance study in healthy volunteers indicated that single intravenous doses of alprostadil from 1 to 120 mcg were well tolerated. Beginning with a 40 mcg bolus intravenous dose, the frequency of drug-related systemic adverse events increased in a dose-dependent manner, characterized mainly by facial flushing. The primary symptom of an edex ® overdose is a prolonged erection or priapism. Because of the potential for tissue hypoxia and possible necrosis, it is strongly recommended to treat an erection lasting more than 6 hours. The patient is strongly encouraged to go to the nearest emergency room if his personal physician is not available. In the event of an overdose, supportive therapy according to the presence of other symptoms is recommended.

HOW SUPPLIED edex ® (alprostadil for injection) is available in single-dose, dual-chamber cartridges intended for use with the reusable edex ® injection device. One chamber of the cartridge contains 10.75, 21.5, or 43 mcg of alprostadil as a white, sterile, lyophilized powder. The other chamber contains 1.075 mL of sterile 0.9% sodium chloride. When the cartridge is placed into the edex ® injection device and reconstituted, the deliverable amount of alprostadil in each milliliter is 10, 20, or 40 mcg, respectively. edex ® Cartridge 2 Pack contains one reusable edex ® injection device, two single-dose, dual-chamber cartridges, two 1⁄2-inch, 29-gauge (0.33 mm × 12.7 mm) needles, and four alcohol swabs. edex ® Cartridge 6 Pack contains one reusable edex ® injection device, six single-dose, dual-chamber cartridges, six 1⁄2-inch, 29-gauge (0.33 mm × 12.7 mm) needles, and twelve alcohol swabs. The edex ® cartridges are supplied in the following packages: edex ® Cartridge 2 Pack (includes one injection device, two cartridges, two needles and four alcohol swabs) 10 mcg 1 × 2 Pack NDC 52244-010-02 20 mcg 1 × 2 Pack NDC 52244-020-02 40 mcg 1 × 2 Pack NDC 52244-040-02 edex ® Cartridge 6 Pack (includes one injection device, six cartridges, six needles and twelve alcohol swabs) 10 mcg 1 × 6 Pack NDC 52244-010-06 20 mcg 1 × 6 Pack NDC 52244-020-06 40 mcg 1 × 6 Pack NDC 52244-040-06 Store at 25°C (77°F); excursions permitted between 15°C - 30°C (59°F - 86°F).